Occurrence of rare earth elements in umbilical cord serum and association with thyroid hormones and birth outcomes in newborns.

Rare earth elements (REEs) are emerging contaminants that are increasingly used in high technology products. However, limited information is available regarding exposure to REEs and associated health effects in neonates. This study aimed to investigate the association between REE concentrations and thyroid hormone levels, as well as birth outcomes in 109 newborns in Beijing, China. We measured the concentrations of 16 REEs and thyroid hormones in umbilical cord serum. To assess the impact of exposure to individual REEs and REE mixtures on thyroid hormone levels and birth outcomes, we employed univariate linear regression, least absolute shrinkage and selection operator (LASSO), and weighted quantile sum (WQS) models. We detected 14 REEs at high rates (92.6%-100%), with yttrium exhibiting the highest median (interquartile range) concentration [43.94 (0.33-172.55) ng/mL], followed by scandium [3.64 (0.46-11.15) ng/mL]. Univariate analyses showed that per logarithmic (ln)-unit change of neodymium (Nd) and samarium (Sm) was associated with 0.039 [95% confidence interval (CI): 0.001, 0.007] and 0.031 (95% CI: 0.003, 0.060) increases in free thyroxine (FT4) levels, respectively. Moreover, 14 REEs exhibited significant associations with triiodothyronine (T3) levels, resulting in increases ranging from 0.066 to 0.307. Elevated concentrations of terbium (Tb) [per ln-unit change: -0.021 (95% CI: -0.041, -0.01)] and lutetium (Lu) [-0.023 (95% CI: -0.043, -0.002)] were inversely correlated with birth length in newborns. A further multiple exposure analysis employing the LASSO model identified Sm, Nd, Y, Sc, and Lu as critical factors influencing FT4 and T3 levels. Additionally, WQS analyses showed positive associations between exposure to a mixture of 14 REEs and FT4 (P = 0.046), T3 (P < 0.001), and birth length (P = 0.049). These findings suggest that in utero exposure to REEs might disrupt thyroid hormone homeostasis and impact intrauterine growth. Further studies are warranted to validate these findings and elucidate the underlying mechanisms.

Concentration of heavy metals and rare earth elements in patients with brain tumours: Analysis in tumour tissue, non-tumour tissue, and blood.

Inorganic elements have been associated with brain tumours for long. The blood concentration of 47 elements was assessed by ICP-MS in 26 brain tumour patients and 21 healthy subjects from Bucharest (Romania). All 47 elements were detected in the brain tumour tissue, and 22 were detected in > 80% of samples; this implies that these elements can cross the blood-brain barrier. Median blood levels of cadmium, lead, and nickel were higher than the reference values (1.14, 53.3, and 2.53 ng/mL). Gadolinium and tantalum showed significantly higher concentrations among cases. We observed considerable differences and different profiles of the presence of inorganic elements between the tumour and non-tumour brain tissue and between tissue from the primary tumour and tissue from brain metastasis. Our data suggest that similar to heavy metals, other elements - commonly used in high tech devices and rare earth elements - can also influence brain tumour.

Early Pregnancy Exposure to Rare Earth Elements and Risk of Gestational Diabetes Mellitus: A Nested Case-Control Study.

Objective: The extensive use of rare earth elements (REEs) in many technologies was found to have effects on human health, but the association between early pregnancy exposure to REEs and gestational diabetes mellitus (GDM) is still unknown. Methods: This nested case-control study involved 200 pregnant women with GDM and 200 healthy pregnant women from the Peking University Birth Cohort in Tongzhou. We examined the serum concentrations of 14 REEs during early pregnancy and analyzed their associations with the risk of GDM. Results: When the elements were considered individually in the logistic regression model, no significant associations were found between REEs and GDM, after adjusting for confounding variables (P > 0.05). In weighted quantile sum (WQS) regression, each quartile decrease in the mixture index for REEs resulted in a 1.67-fold (95% CI: 1.12-2.49) increased risk of GDM. Neodymium (Nd), Praseodymium (Pr), and Lanthanum (La) were the most important contributors in the mixture. Conclusion: The study findings indicated that early pregnancy exposure to lower levels of REE mixture was associated with an increased risk of GDM, and Nd, Pr, and La exhibited the strongest effects in the mixture.

Concentrations of rare earth elements in maternal serum during pregnancy and risk for fetal neural tube defects.

Rare earth elements (REEs) are ubiquitous in the environment. Animal experiments have shown that many REEs have adverse impacts on the health of fetuses. However, data from humans are scarce. In this study, we examined the associations between concentrations of 10 REEs in maternal serum and the risk for fetal neural tube defects (NTDs). The study included 200 pregnant women with pregnancies affected by NTDs and 400 pregnant women with healthy fetuses/infants. Fifteen REEs in maternal serum were assessed; 10 of them were detectable in over 60% of samples and were included in statistical analyses, including lanthanum (La), cerium (Ce), praseodymium (Pr), neodymium (Nd), samarium (Sm), europium (Eu), terbium (Tb), dysprosium (Dy), lutetium (Lu), and yttrium (Y). When the elements were considered individually with the use of Logistic regression model, the risk for NTDs increased by 2.78-fold (1.25-6.17) and 4.31-fold (1.93-9.62) for La, and 1.52-fold (0.70-3.31) and 4.73-fold (2.08-10.76) for Ce, in the second and third tertiles, respectively, compared to the lowest concentration tertile. When Bayesian kernel machine regression was used to examine the joint effect of exposure to all 10 REEs, the risk for NTDs increased with overall levels of these REEs and the association between La and NTD risk remained when other nine elements were taken into consideration simultaneously. Taken together, this study shows that the risk for NTDs increases with La concentrations when single REEs are considered and with concentrations of all 10 REEs when these REEs are considered as a co-exposure mixture.

Association of blood chromium and rare earth elements with the risk of DNA damage in chromate exposed population.

Pollution of heavy metals often occurs in combination with multiple metal ions. Whether the genetic damage among chromate exposed population correlated with rare earth elements (REEs) was still not well elucidated. A total of 291 participants from a chromate production plant were recruited in the present study. The DNA oxidative damage was evaluated by urinary 8-hydroxydeoxyguanosine (8-OHdG) and the concentrations of chromium (Cr) and 15 REEs accumulated in the peripheral blood of participants were determined. The results showed that significant DNA oxidative damage was observed in chromate exposed workers. Blood REEs levels in the exposed group were significantly higher than the control group and blood REEs increased in a concentration dependent manner with Cr. Additionally, significant correlations were observed between blood Cr and 10 REEs concentrations. Blood Cr had a significant positive correlation with urinary 8-OHdG. Blood Cr and Yttrium had a positive interactive effect on urinary 8-OHdG. Collectively, the results suggested workers who had been working in the chromate plant were simultaneously exposed to chromate and a variety of REEs, which could have interactive effects on the DNA damage of workers.

Body burden of toxic metals and rare earth elements in non-smokers, cigarette smokers and electronic cigarette users.

Smoking is considered an important source for inorganic elements, most of them toxic for human health. During the last years, there has been a significant increase in the use of e-cigarettes, although the role of them as source of inorganic elements has not been well established. A cross-sectional study including a total of 150 subjects from Brasov (Romania), divided into three groups (non-smokers, cigarette smokers and electronic cigarettes smokers) were recruited to disclose the role of smoking on the human exposure to inorganic elements. Concentration of 42 elements, including trace elements, elements in the ATSDR's priority pollutant list and rare earth elements (REE) were measured by ICP-MS in the blood serum of participants. Cigarette smokers showed the highest levels of copper, molybdenum, zinc, antimony, and strontium. Electronic cigarette (e-cigarette) users presented the highest concentrations of selenium, silver, and vanadium. Beryllium, europium and lanthanides were detected more frequently among e-cigarette users (20.6%, 23.5%, and 14.7%) than in cigarette smokers (1.7%, 19.0%, and 12.1%, respectively); and the number of detected REE was also higher among e-cigarette users (11.8% of them showed more than 10 different elements). Serum levels of cerium and erbium increased as the duration of the use of e-cigarettes was longer. We have found that smoking is mainly a source of heavy metals while the use of e-cigarettes is a potential source of REE. However, these elements were detected at low concentrations.

[An investigation of lanthanum and other metals levels in blood, urine and hair among residents in the rare earth mining area of a city in China].

Objective: To investigate the levels of lanthanum, cerium, praseodymium, and neodymium in the blood, urine, and hair samples from residents in the rare earth mining area of a city in China, and to provide a scientific basis for the control of rare earth pollution and the protection of population health. Methods: A total of 147 residents who had lived in the rare earth mining area of a city for a long time were selected as the exposure group, and 108 residents in Guyang County of this city who lived 91 km away from the rare earth mining area were selected as the control group. Blood, urine, and hair samples were collected from the residents in both groups. Inductively coupled plasma mass spectrometry was used to determine the content of lanthanum, cerium, praseodymium, and neodymium in blood, urine, and hair samples. Results: In the exposure group, the median levels of lanthanum, cerium, praseodymium, and neodymium were 0.854, 1.724, 0.132, and 0.839 µg/L, respectively, in blood samples, 0.420, 0.920, 0.055, and 0.337 µg/L, respectively, in urine samples, and 0.052, 0.106, 0.012, and 0.045 µg/g, respectively, in hair samples. The exposure group had significantly higher levels of the four rare earth elements in blood, urine, and hair samples than the control group (P<0.01) . Conclusion: The residents in the rare earth mining area of this city have higher content of lanthanum, cerium, praseodymium, and neodymium in blood, urine, and hair than those in the non-mining area; the content of cerium is highest, followed by lanthanum, neodymium, and praseodymium.

Blood levels of toxic metals and rare earth elements commonly found in e-waste may exert subtle effects on hemoglobin concentration in sub-Saharan immigrants.

Pollution by heavy metals and more recently by rare earth elements (REE) and other minor elements (ME) has increased due in part to their high use in technological and electronic devices. This contamination can become very relevant in those sites where e-waste is improperly processed, as it is the case in many countries of the African continent. Exposure to some toxic elements has been associated to certain hematological disorders, specifically anemia. In this study, the concentrations of 48 elements (including REE and other ME) were determined by ICP-MS in whole blood samples of sub-Saharan immigrants with anemia (n=63) and without anemia (n=78). We found that the levels of Fe, Cr, Cu, Mn, Mo, and Se were significantly higher in the control group than in the anemia group, suggesting that anemia was mainly due to nutritional deficiencies. However, since other authors have suggested that in addition to nutritional deficiency, exposure to some elements may influence hemoglobin levels, we wanted to explore the role of a broad panel of toxic and "emerging" elements in hemoglobin deficiency. We found that the levels of Ag, As, Ba, Bi, Ce, Eu, Er, Ga, La, Nb, Nd, Pb, Pr, Sm, Sn, Ta, Th, Tl, U and V were higher in anemic participants than in controls. For most of these elements an inverse correlation with hemoglobin concentration was found. Some of them also correlated inversely with blood iron levels, pointing to the possibility that a higher rate of intestinal uptake of these could exist in relation to a nutritional deficiency of iron. However, the higher levels of Pb, and the group of REE and other ME in anemic participants were independent of iron levels, pointing to the possibility that these elements could play a role in the development of anemia.

Effect of rare earth elements on beef cattle growth performance, blood clinical chemical parameters and mitogen stimulated proliferation of bovine peripheral blood mononuclear cells in vitro and ex vivo.

Rare earth elements (REE) are possible performance enhancers in animal production, but little is known about their effects on ruminants. Therefore a feeding trial was conducted with 40 fattening bulls who received 0, 100, 200 or 300mg REE-citrate/kg dry matter (DM), containing 34.30% La, 58.09% Ce and 7.61% other REE. DM intake was measured daily and live weight weekly. Ex vivo ConcanavalinA (ConA)-stimulated cell proliferation of peripheral blood mononuclear cells (PBMC) was tested by MTT and alamar blue (AB) assay. Serum was analysed for clinical chemical parameters, ion (Mg, Ca and P) and REE concentrations. The effects of LaCl(3), CeCl(3), NdCl(3) and YCl(3) on ConA-stimulated proliferation of PBMC were tested in vitro, using MTT and AB assay. REE-citrate supplementation did affect DM intake, but not live weight gain, clinical chemical parameters, and ion concentrations significantly. In REE-300 group ex vivo proliferation of PBMC was significantly increased. In vitro ConA-stimulated proliferation decreased with rising REE-chloride concentrations. At least at the highest tested concentration (approximately 290µM) the inhibition reached significance. Proliferation of non-stimulated PBMC was not affected dose-dependently. REE affect the proliferation of PBMC, thus an effect on the bovine immune system is possible. However, the great differences in effective doses in vitro and ex vivo (serum REE concentrations) might explain the different results from the experiments.

[Correlation of light rare earth elements in rats hair, blood and organs].

OBJECTIVE: To study the correlation of rare earth elements (REEs) in the rats' hair, blood and organs. METHODS: Based on the level of animal weights, 50 healthy male SD rats were randomly divided into five groups including control group and four Citrate REEs level groups (low, middle, high-I and high-II). Before the experiment, the hair of rats' back was eliminated. After the rats were fed for four weeks, the fresh hair of the rats was collected. Except the high-II group, the blood and organs of the others were collected. The high-II group was fed for other four weeks without Citrate REEs. At the end of eighth week, hair, blood and organs of the high-II group were collected. Determination of light REEs concentration in the rats' hair, blood, liver, spleen and bone by ICP-MS. RESULTS: The correlation coefficients of REEs concentration between hair and organs (such as liver, spleen and bone) were more than 0.5, while those of REEs concentration between blood and organs (such as liver spleen and bond) were less than 0.5. In the group H- Il, the Rees concentration in blood, hair, liver, spleen and bone were all decrease, and the REEs concentration of blood was close to that of the control groups. CONCLUSION: The concentrations of REEs in these organs were different. And hair was better than blood as a biomarker to reflect body exposure of REEs.

Development of an in vitro model for assessing the in vivo stability of lanthanide chelates.

An in vitro model was developed to evaluate the in vivo stability of lanthanide polyaminocarboxylate complexes. The ligand-to-metal ratios for the chelates EDTA, CDTA, DTPA, MA-DTPA (monoamide-DTPA) and DOTA with the lanthanides lanthanum, samarium, and lutetium were optimized to achieve > or = 98% complexation yield for the resultant radiolanthanide complexes. The exchange of the radiolanthanides from their EDTA, CDTA, DTPA, MA-DTPA and DOTA complexes with Ca(2+) was determined by in vitro adsorption and in vitro column studies using hydroxyapatite (HA), an in vitro bone model. In vitro serum stability of these radiolanthanide complexes was used as an additional indicator of in vivo stability, although the mechanism of instability in serum will be different than with bone. The in vitro studies were consistent with the expected findings that the smallest lanthanide (Lu) formed the most stable complexes. In vivo studies were done to validate the in vitro model. Biodistribution studies in normal CF-1 mice showed that in vivo stability of the complex (i.e., the more lanthanide remaining in complex form) could be assessed by a combination of the urinary, bone and liver uptake. For example, biodistribution studies demonstrate that high urinary excretion correlated with complex stability, while high liver plus bone uptake correlated with complex instability. The urinary excretion of the EDTA complexes decreased from (177)Lu to (140)La indicating a loss in stability in the direction of (140)La, consistent with the in vitro studies. The more stable a lanthanide complex is, the lower its exchange with HA in vitro will be, and the lower its combined bone plus liver uptake and higher its urinary excretion will be in vivo. This investigation indicates that the in vivo stability can be determined by a screening method that measures the degree of exchange from the lanthanide chelate with hydroxyapatite (HA) and its serum stability.

Lanthanides enhance pulmonary absorption of insulin.

In an effort to investigate the enhancement effect of lanthanide ions (Ln3+) on the absorption of larger molecules from the pulmonary pathway, insulin (mol. wt. = 5730) was chosen as a model peptide. The absorption of insulin preadministered or coadministered with Ln3+ from the lung was investigated by means of an in situ pulmonary absorption experiment. The enhancement absorption of insulin by Ln3+ ions was evaluated by calculating the various bioavailabilities (Fr) of insulin from pulmonary absorption. Moreover, the temporal change of Gd content in serum was also investigated. Results showed that the promoting effect of Ln3+ on the bioavailability of insulin is closely related to its species, concentration, and delivery order. The effect of the median Ln3+ series was remarkably greater than that of light and heavy Ln3+. The anionic form of Gadolinium (Fr = 68.4%) seemed to be more effective compared with its cationic form (Fr = 59.5%). Coadministration of Gd3+ with insulin (Fr = 80.1%) was the most effective in increasing insulin absorption from the lung. Gd3+ was rapidly absorbed and metabolized to a normal level after 4 h. It was suggested that lanthanides in a very low concentration might become potent absorption enhancers to improve absorption of larger molecules via the pulmonary pathway.

Determination of rare earth elements in human blood serum by inductively coupled plasma mass spectrometry after chelating resin preconcentration.

The determination of all rare earth elements (REEs) in human blood serum by inductively coupled plasma mass spectrometry (ICP-MS) was performed with the aid of chelating resin (Chelex 100) preconcentration after acid digestion with HNO3 and HClO4. When chelating resin preconcentration was carried out at room temperature, the recoveries of heavy REEs were lower than those of light REEs because of their stable complex formation with residual organic compounds remaining in the digested serum solution. These problems were overcome by heating the solution at 80 degrees C during the chelating resin preconcentration process. As a result, the recoveries for all REEs were improved to 92-102% in the case of a concentration factor of 4, where the analytical detection limits for REEs were below 0.2 x 10(-12) g ml-1. Consequently, all REEs in individual human blood sera collected from five healthy volunteers could be determined by ICP-MS with good precision. The concentrations of REEs in human blood serum were extremely low, in the range from ca. 1 x 10(-12) g ml-1 of Eu to ca. 230 x 10(-12) g ml-1 of Ce.

[Determination of ultra-trace rare-earth elements in human plasma by inductively coupled plasma mass spectrometry].

Inductively coupled plasma mass spectrometry (ICP-MS), highly sensitive inorgnic analytic technique, fits to determine ultra-trace rare-earth elements in human plasma. Under the optimized conditions detection limits for 15 rare-earth elements are in the range of 0.7 (for Eu)-5.4 (for Gd) ng.L-1. Indium as an internal standard element is used to compensate for matrix suppression effect and sensitivity drift. Three kinds of preparation methods, diluted with 1% HNO3, digested with HNO3-H2O2 and with HNO3-HClO4, are checked and compared, and the former is the simplest way to be measured. The samples diluted with 1% HNO3, stored in 4 degrees C, are very steady for 16 days. With the method, 11 healthy plasma samples in Changchun area of China are analysed.

Determination of rare earth elements in blood serum reference sample by chelating resin preconcentration and inductively coupled plasma mass spectrometry.

Rare earth elements (REEs) in a blood serum reference sample, which is a freeze-dried sample issued from the National Institute for Environmental Studies, Japan, have been determined by inductively coupled plasma mass spectrometry (ICP-MS) after sample digestion and concentration pretreatment. The freeze-dried serum sample (ca. 0.8 g), which corresponded to 10 ml of original blood serum, was digested with HNO3 with heating on a hot plate. The digested sample was then diluted with 100 ml of 0.1 M HNO3, and REEs in the diluted solution were adsorbed on chelating resin (Chelex 100). The resin was then filtered with a glass filter. Finally, REEs on the resin were dissolved with 10 ml of 2 M HNO3 aqueous solution, and the sample solution was analyzed by ICP-MS. The concentrations of all the REEs were successfully determined by the present method. The recovery values of REEs were in the range of 70-80%, and the relative standard deviation of the recovery values in repeated experiments (n = 3) was less than 5% for all REEs. In addition, 20 other elements were also determined by ICP-MS and ICP-AES.

Plasma and synovial fluid lanthanides in rheumatoid arthritis: variations after intra-articular therapy.

Lanthanides (Ln), or rare earth elements, are detectable in trace amounts in organisms. Increased concentrations of Ln have been observed in rheumatoid arthritis (RA) in plasma (pl) and synovial fluid (Sf). We have evaluated pl and Sf concentrations of Ln (in particular La, Nd, Ce, Yb, Lu, Eu), in rheumatoid arthritis patients, before and after intra-articular steroid injection. Increased pl and Sf concentrations of Ln were confirmed in RA. No detectable synovial fluid concentrations of Ln were observed in healthy controls. A statistically significant Ln reduction (p less than 0.001) was observed in Sf 3 and 6 days after local steroid injection and in pl after 6 days. The decrease in Ln concentrations in Sf and pl, after antiphlogistic therapy, reflects the reduction of the inflammatory condition.

Plasma and tissue levels of some lanthanide elements in malignant and non-malignant human tissues.

Lanthanum (La) levels in plasma, in erythrocyte hemolysate and in tissue from healthy subjects and patients with laryngeal carcinoma were determined by neutron activation analysis. Plasma lanthanum levels were significantly higher in laryngeal carcinomas than in either healthy controls or in subjects suffering from localized inflammation (e.g. epicondylitis of the elbow) (p less than 0.001). The mean La concentration in malignant tissue samples was 57.5 +/- 7.2 ng g-1; the corresponding level in normal adjacent tissue from the same organ was 94.6 +/- 12.0 ng g-1. This 61% decrease in the concentration of La in malignant tissues was highly significant (p less than 0.001). In patients with laryngeal carcinoma we did not observe any detectable level of lanthanum in erythrocyte hemolysate; the mean La erythrocyte hemolysate level in healthy controls and in patients suffering from localized inflammatory condition was 14.3 and 33.2 ng ml-1, respectively. Further studies are in progress to evaluate whether or not this element can serve as a marker for diagnosis or prognosis in cancer.